Potential option for rabies post-exposure prophylaxis: New vaccine with PIKA adjuvant against diverse Chinese rabies strains.

Rabies is a fatal zoonotic disease caused by the rabies virus. Despite existing vaccines, failures still persist. Complete protection relies on improving vaccination for delayed antibody response and weak cellular immunity. A more effective and secure vaccine is necessary for rabies prevention. For this purpose, we employed the use of PIKA adjuvant, a stabilized double-stranded RNA that interacts with TLR3, as an enhancer for the rabies immunization. Testing on mice infected with seven rabies strains prevalent in China showed over 80% protective efficacy without immunoglobulin. In contrast, the PIKA rabies vaccine exhibited a more significant enhancement in neutralizing antibody levels just 5 days post-vaccination, surpassing the immune response induced by licensed rabies vaccines. Furthermore, the administration of the PIKA rabies vaccine resulted in a significant augmentation in the population of T cells that produce IFN-γ in response to the antigen. Additionally, elevated levels of IL-1ß, IL-6, CCL-2, and TNF-α were observed at the injection site. Furthermore, an increase in the levels of chemotactic proteins and pro-inflammatory molecules in the serum was observed following administration of the PIKA rabies vaccine. Confirmation of the mechanism of action of PIKA was further established by testing it on TLR3-knockout mice, proving that its adjuvant function is dependent on the TLR3 pathway. Taken together, these results indicate that the PIKA vaccine for rabies shows potential as a highly efficacious approach, resulting in a significant enhancement of the efficacy of rabies vaccines.

The effect of layer thickness ratio on the drug release behavior of alternating layered composite prepared by layer-multiplying co-extrusion.

Multi-layered drug delivery (MLDD) system has promising potential to achieve controlled release. However, existing technologies face difficulties in regulating the number of layers and layer-thickness ratio. In our previous works, layer-multiplying co-extrusion (LMCE) technology was applied to regulate the number of layers. Herein, we utilized layer-multiplying co-extrusion technology to modulate the layer-thickness ratio to expand the application of LMCE technology. Four-layered poly (ε-caprolactone)-metoprolol tartrate/poly (ε-caprolactone)-polyethylene oxide (PCL-MPT/PEO) composites were continuously prepared by LMCE technology, and the layer-thickness ratios for PCL-PEO layer and PCL-MPT layer were set to be 1:1, 2:1, and 3:1 just by controlling the screw conveying speed. The in vitro release test indicated that the rate of MPT release increased with decreasing the thickness of the PCL-MPT layer. Additionally, when PCL-MPT/PEO composite was sealed by epoxy resin to eliminate the edge effect, sustained release of MPT was achieved. The compression test confirmed the potential of PCL-MPT/PEO composites as bone scaffolds.

Advances in hydrogels for the treatment of periodontitis.

Periodontitis is the second most prevalent oral disease and can cause serious harm to human health. Hydrogels are excellent biomaterials that can be used for periodontitis as drug delivery platforms to achieve inflammation control through high drug delivery efficiency and sustained drug release and as tissue scaffolds to achieve tissue remodelling through encapsulated cell wrapping and effective mass transfer. In this review, we summarize the latest advances in the treatment of periodontitis with hydrogels. The pathogenic mechanisms of periodontitis are introduced first, followed by the recent progress of hydrogels in controlling inflammation and tissue reconstruction, in which the specific performance of hydrogels is discussed in detail. Finally, the challenges and limitations of hydrogels for clinical applications in periodontitis are discussed and possible directions for development are proposed. This review aims to provide a reference for the design and fabrication of hydrogels for the treatment of periodontitis.

Experience of a modified chest tube suture-fixation technique in uniportal thoracoscopic pulmonary resection.

OBJECTIVE: This study aimed to explore the feasibility and advantages of a modified chest tube suture-fixation technique in uniportal video-assisted thoracic surgery for pulmonary resection. METHODS: A retrospective analysis was conducted on 116 patients who underwent uniportal video-assisted thoracic surgery (U-VATS) for lung diseases in Zhengzhou People's Hospital between October 2019 and October 2021. Patients were stratified into two groups based on the applied suture-fixation methods, i.e., 72 patients in the active group and 44 patients in the control group. The two groups were subsequently compared in the terms of gender, age, operation method, indwelling time of chest tube, postoperative pain score, chest tube removal time, wound healing grade, length of hospital stay, incision healing grade, and patient satisfaction. RESULTS: There was no significant difference between the two groups in terms of gender, age, operation method, indwelling time of chest tube, postoperative pain score, and length of hospital stay (P = 0.167, 0.185, 0.085, 0.051, 0.927, and 0.362, respectively). However, the chest tube removal time, incision healing grade, and incision scar satisfaction in the active group were significantly better compared with those of the control group (P = < 0.001, 0.033, and < 0.001, respectively). CONCLUSION: In summary, the new suture-fixation approach can minimize the number of stitches, and time necessary for chest tube removal process, and avoid the pain experienced when removing the drainage tube. This method is more feasible, has better incision conditions, and provides a convenient tube removal, making it more suitable to patients.

Celastrol-encapsulated microspheres prepared by microfluidic electrospray for alleviating inflammatory pain.

Inflammatory pain is induced by trauma, infection, chemical stimulation, etc. It causes severe physical and psychological agony to patients. Celastrol has powerful anti-inflammatory property and has achieved good results in various inflammation-related diseases. However, the low water solubility and multi-system toxicity limit its clinical application. Herein, we proposed alginate microspheres with core-shell structure which encapsulated celastrol by microfluidic electrospray to effectively overcome the shortcomings and improve the therapeutic effect. The microspheres had uniform size and good biocompatibility, and could release the loaded drugs in the gut. The behavioral tests showed that the celastrol-loaded microspheres effectively alleviated inflammatory pain, and the hematoxylin and eosin staining (HE staining), immunofluorescence and detection of inflammatory cytokines showed the anti-inflammatory effect. These results indicated that the microspheres could reduce dose and toxicity without affecting efficacy, and facilitate the application of celastrol in different clinical situations.

Paraganglioma of the anterior superior mediastinum: Presentation of a case of mistaken diagnosis so long and review of the literature.

INTRODUCTION AND IMPORTANCE: Mediastinal paraganglioma is a rare tumor with neuroendocrine activity, highly susceptible to misdiagnosis. Herein, we present a case misdiagnosed as Castleman disease for nearly a decade, significantly enlarged, lost the opportunity of thoracoscopic surgery, and was removed by median thoracotomy. CASE PRESENTATION: A 59-year-old woman complained of having a mediastinal mass, was diagnosed with Castleman disease for nearly a decade and was admitted to the hospital due to neck tightness. The tumor size was significantly enlarged. We proceeded to interventional angiography with gelatin sponge angioembolization, and the tumor was resected through a median sternotomy on the second day. The operation was smooth, and the tumor was gray and slightly brittle. Postoperative pathology confirmed paraganglioma; lymph node metastasis was not detected (0/3). CLINICAL DISCUSSION: Mediastinal paraganglioma is a rare tumor and can be either functional or nonfunctional. It can be differentiated from many diseases. The SSTR-PET-CT labeled with 68Ga-somatostatin analog, plasma metanephrine, and normetanephrine are essential for the diagnosis. Surgical resection is the most effective form of treatment. Pre-operative embolization of the feeding artery is considered to have a low rate of intraoperative bleeding. We recommend making comprehensive preparations to ensure perioperative safety and long-term survival. CONCLUSION: When a vascularized mass is discovered in the mediastinum, surgeons should consider the possibility of a paraganglioma. Multidisciplinary consultation should be involved in the formulation of treatment plans. Lifelong surveillance for residual tumor growth and recurrence is required.

Application of bilateral simultaneous sequential single-incision video-assisted thoracic surgery in multiple nodules both lungs: a single-center experience of 10 cases.

OBJECTIVE: To discuss the application of bilateral simultaneous sequential single-incision video-assisted thoracic surgery in multiple nodules in both lungs. METHODS: A retrospective analysis of 10 patients in Zhengzhou People's Hospital who underwent single-incision thoracoscopic surgery to treat multiple nodules in both lungs at the same time from September 2019 to January 2021, and analyze the perioperative indicators (general condition, smoking history, family history, follow-up time of pulmonary nodules, size, location, height and weight, pulmonary function, intraoperative blood loss, operation time, color and volume of drainage fluid, catheterization time, perioperative complications, length of stay, pathology, patient satisfaction, etc.). RESULTS: All 10 patients used single-incision thoracoscopy to complete bilateral simultaneous sequential operations, aged 32 to 70 years, 8 female patients, 2 male patients, preoperative follow-up time ranging from 1 day to 2 years, a total of 23 lung nodules were removed except for the benign lesions in one nodule in the 2 patients, the other nodules were tumorous lesions (91.3%). The average total hospital stay was 10.5 days (8-14 days), and the average operation time was 194.5 min (145-292 min). The blood loss ranged from 10 to 280 ml, all patients had no serious complications during the perioperative period, and they recovered well and were discharged smoothly, and the satisfaction reached 100%. CONCLUSION: Single-incision bilateral simultaneous sequential thoracoscopy have certain advantages in the treatment of patients with multiple nodules in both lungs, conforms to the concept of rapid recovery, and is a feasible choice in the shared decision making of doctors and patients.

A Method for Identifying the Spatial Range of Mining Disturbance Based on Contribution Quantification and Significance Test.

Identifying the spatial range of mining disturbance on vegetation is of significant importance for the plan of environmental rehabilitation in mining areas. This paper proposes a method to identify the spatial range of mining disturbance (SRMD). First, a non-linear and quantitative relationship between driving factors and fractional vegetation cover (FVC) was constructed by geographically weighted artificial neural network (GWANN). The driving factors include precipitation, temperature, topography, urban activities, and mining activities. Second, the contribution of mining activities (Wmine) to FVC was quantified using the differential method. Third, the virtual contribution of mining activities (V-Wmine) to FVC during the period without mining activity was calculated, which was taken as the noise in the contribution of mining activities. Finally, the SRMD in 2020 was identified by the significance test based on the Wmine and noise. The results show that: (1) the mean RMSE and MRE for the 11 years of the GWANN in the whole study area are 0.0526 and 0.1029, which illustrates the successful construction of the relationship between driving factors and FVC; (2) the noise in the contribution of mining activities obeys normal distribution, and the critical value is 0.085 for the significance test; (3) most of the SRMD are inside the 3 km buffer with an average disturbance distance of 2.25 km for the whole SRMD, and significant directional heterogeneity is possessed by the SRMD. In conclusion, the usability of the proposed method for identifying SRMD has been demonstrated, with the advantages of elimination of coupling impact, spatial continuity, and threshold stability. This study can serve as an early environmental warning by identifying SRMD and also provide scientific data for developing plans of environmental rehabilitation in mining areas.

Hydrogen sulfide ameliorated lipopolysaccharide-induced acute lung injury by inhibiting autophagy through PI3K/Akt/mTOR pathway in mice.

OBJECTIVE: Recent studies reported that hydrogen sulfide (H2S) is an effective agent for the prevention and treatment of acute lung injury (ALI). But the underlying mechanisms have not been understood clearly. In this study, we explored the possible mechanism from the perspective of autophagy regulation. METHODS: A mouse model of ALI and alveolar type II epithelial cells (MLE-12 cells) injury was induced using lipopolysaccharide (LPS). Expression of Beclin 1 and the conversion of LC3I to LC3II were detected to evaluate the activity of autophagy. Lung histopathological changes, wet/dry (W/D) ratio, pro-inflammatory cytokines TNF-α, IL-1ß and protein content in bronchoalveolar lavage fluid (BALF), cell viability and lactic dehydrogenase (LDH) in the culture medium were determined to evaluate the severity of ALI. The activity of PI3K/Akt/mTOR pathway was detected to explore the possible mechanisms involved in the regulation of autophagy by H2S. RESULTS: The expression of Beclin 1 and the conversion of LC3I to LC3II were significantly increased after LPS treatment and reversed by H2S both in vivo and in vitro. Lung histopathological changes, W/D ratio, TNF-α, IL-1ß and protein content in BALF induced by LPS were effectively ameliorated by H2S and autophagy inhibitor 3-methyladenine. The in vitro results showed that H2S and 3-methyladenine also attenuated LPS-induced cell viability decrease and LDH release. Furthermore, H2S effectively reversed LPS-induced PI3K/Akt/mTOR signaling pathway inhibition. CONCLUSION: Autophagy inhibition through PI3K/Akt/mTOR pathway was involved in H2S prevention of LPS-induced ALI in mice.